{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T01:57:50Z","timestamp":1793239070122,"version":"4.5.0"},"reference-count":63,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:00:00Z","timestamp":1755907200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T00:00:00Z","timestamp":1755907200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000025","name":"U.S. Department of Health & Human Services | NIH | National Institute of Mental Health","doi-asserted-by":"publisher","award":["UH2 MH109334"],"award-info":[{"award-number":["UH2 MH109334"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000025","name":"U.S. Department of Health & Human Services | NIH | National Institute of Mental Health","doi-asserted-by":"publisher","award":["UH3 MH109334"],"award-info":[{"award-number":["UH3 MH109334"]}],"id":[{"id":"10.13039\/100000025","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Commun Biol"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Cognitive flexibility broadly describes behavioral alterations made in response to environmental changes and is fundamental for survival. While human and non-human animal assessments of cognitive flexibility are available, a systematic cross-species comparison of behavioral, neurophysiological, and computational markers of cognitive flexibility has not been reported. Using versions of a probabilistic reversal learning task aligned between humans and rats, electroencephalogram recordings reveal a frontal reward positivity (RewP) associated with unexpected reward outcomes. Reinforcement Q-learning models of both species\u2019 task behavior reveal that prediction error (PE) magnitude was significantly related to RewP amplitude. The stimulant drug modafinil alters PEs in rats without affecting the RewP in either species. These findings reveal analogous neurophysiological markers associated with PEs in humans and rats using equivalent tasks and identical computational analyses. This translational approach may improve the predictive validity of tests for novel pharmacotherapies and accelerate neuropsychiatric treatment by assessing neural mechanisms conserved across species.<\/jats:p>","DOI":"10.1038\/s42003-025-08729-x","type":"journal-article","created":{"date-parts":[[2025,8,23]],"date-time":"2025-08-23T10:13:49Z","timestamp":1755944029000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of conserved frontal neurophysiological markers of cognitive flexibility in humans and rats"],"prefix":"10.1038","volume":"8","author":[{"given":"Andre","family":"Der-Avakian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel A.","family":"Barnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7321-2704","authenticated-orcid":false,"given":"Ty","family":"Lees","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans S.","family":"Schroder","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4597-9801","authenticated-orcid":false,"given":"Brian D.","family":"Kangas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7512-1585","authenticated-orcid":false,"given":"Samantha R.","family":"Linton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3788-2919","authenticated-orcid":false,"given":"Stefanie","family":"Nickels","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mykel A.","family":"Robble","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah","family":"Breiger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann M.","family":"Iturra-Mena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Lobien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Perlo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilia F.","family":"C\u00e1rdenas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genevieve P.","family":"Nowicki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyun","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyi","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1977-700X","authenticated-orcid":false,"given":"Daniel G.","family":"Dillon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5814-8062","authenticated-orcid":false,"given":"James P.","family":"Kesby","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Bergman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr","given":"William A.","family":"Carlezon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria B.","family":"Risbrough","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3203-9535","authenticated-orcid":false,"given":"Eran","family":"Mukamel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3367-6536","authenticated-orcid":false,"given":"Stefan","family":"Leutgeb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7772-1143","authenticated-orcid":false,"given":"Diego A.","family":"Pizzagalli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,8,23]]},"reference":[{"key":"8729_CR1","doi-asserted-by":"publisher","first-page":"405","DOI":"10.2307\/2785779","volume":"25","author":"WA Scott","year":"1962","unstructured":"Scott, W. A. Cognitive complexity and cognitive flexibility. Sociometry 25, 405 (1962).","journal-title":"Sociometry"},{"key":"8729_CR2","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1038\/s41583-021-00428-w","volume":"22","author":"LQ Uddin","year":"2021","unstructured":"Uddin, L. Q. Cognitive and behavioural flexibility: neural mechanisms and clinical considerations. Nat. Rev. Neurosci. 22, 167\u2013179 (2021).","journal-title":"Nat. Rev. Neurosci."},{"key":"8729_CR3","doi-asserted-by":"publisher","first-page":"5436","DOI":"10.1093\/cercor\/bhac431","volume":"33","author":"K Z\u00fchlsdorff","year":"2023","unstructured":"Z\u00fchlsdorff, K., Dalley, J. W., Robbins, T. W. & Morein-Zamir, S. Cognitive flexibility: neurobehavioral correlates of changing one\u2019s mind. Cereb. Cortex 33, 5436\u20135446 (2023).","journal-title":"Cereb. Cortex"},{"key":"8729_CR4","doi-asserted-by":"publisher","first-page":"380","DOI":"10.1080\/02699931.2010.491647","volume":"25","author":"JJ Genet","year":"2011","unstructured":"Genet, J. J. & Siemer, M. Flexible control in processing affective and non-affective material predicts individual differences in trait resilience. Cogn. Emot. 25, 380\u2013388 (2011).","journal-title":"Cogn. Emot."},{"key":"8729_CR5","doi-asserted-by":"publisher","first-page":"474","DOI":"10.1016\/j.neuroimage.2014.08.008","volume":"102","author":"Q Chen","year":"2014","unstructured":"Chen, Q. et al. Association of creative achievement with cognitive flexibility by a combined voxel-based morphometry and resting-state functional connectivity study. Neuroimage 102, 474\u2013483 (2014).","journal-title":"Neuroimage"},{"key":"8729_CR6","doi-asserted-by":"crossref","unstructured":"Cools, R. Neuropsychopharmacology of Cognitive Flexibility. In Brain Mapping 349\u2013353 (Elsevier, 2015).","DOI":"10.1016\/B978-0-12-397025-1.00253-0"},{"key":"8729_CR7","doi-asserted-by":"publisher","unstructured":"Gabrys, R. L., Tabri, N., Anisman, H. & Matheson, K. Cognitive control and flexibility in the context of stress and depressive symptoms: the cognitive control and flexibility questionnaire. Front. Psychol. https:\/\/doi.org\/10.3389\/fpsyg.2018.02219 (2018).","DOI":"10.3389\/fpsyg.2018.02219"},{"key":"8729_CR8","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1186\/1471-2318-10-16","volume":"10","author":"JC Davis","year":"2010","unstructured":"Davis, J. C., Marra, C. A., Najafzadeh, M. & Liu-Ambrose, T. The independent contribution of executive functions to health related quality of life in older women. BMC Geriatr. 10, 16 (2010).","journal-title":"BMC Geriatr."},{"key":"8729_CR9","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1176\/appi.ajp.2011.11010137","volume":"169","author":"OJ Robinson","year":"2012","unstructured":"Robinson, O. J., Cools, R., Carlisi, C. O., Sahakian, B. J. & Drevets, W. C. Ventral striatum response during reward and punishment reversal learning in unmedicated major depressive disorder. Am. J. Psychiatry 169, 152\u2013159 (2012).","journal-title":"Am. J. Psychiatry"},{"key":"8729_CR10","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1016\/j.neuroimage.2008.05.049","volume":"42","author":"JV Taylor Tavares","year":"2008","unstructured":"Taylor Tavares, J. V. et al. Neural basis of abnormal response to negative feedback in unmedicated mood disorders. Neuroimage 42, 1118\u20131126 (2008).","journal-title":"Neuroimage"},{"key":"8729_CR11","doi-asserted-by":"publisher","first-page":"587","DOI":"10.1080\/01688639708403745","volume":"19","author":"HOF Veiel","year":"1997","unstructured":"Veiel, H. O. F. A preliminary profile of neuropsychological deficits associated with major depression. J. Clin. Exp. Neuropsychol. 19, 587\u2013603 (1997).","journal-title":"J. Clin. Exp. Neuropsychol."},{"key":"8729_CR12","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1093\/schbul\/sbv226","volume":"42","author":"LF Reddy","year":"2016","unstructured":"Reddy, L. F., Waltz, J. A., Green, M. F., Wynn, J. K. & Horan, W. P. Probabilistic Reversal Learning in Schizophrenia: Stability of Deficits and Potential Causal Mechanisms. Schizophr. Bull. 42, 942\u2013951 (2016).","journal-title":"Schizophr. Bull."},{"key":"8729_CR13","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1016\/j.schres.2007.03.010","volume":"93","author":"JA Waltz","year":"2007","unstructured":"Waltz, J. A. & Gold, J. M. Probabilistic reversal learning impairments in schizophrenia: further evidence of orbitofrontal dysfunction. Schizophr. Res. 93, 296\u2013303 (2007).","journal-title":"Schizophr. Res."},{"key":"8729_CR14","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1176\/ajp.2006.163.7.1282","volume":"163","author":"SR Chamberlain","year":"2006","unstructured":"Chamberlain, S. R., Fineberg, N. A., Blackwell, A. D., Robbins, T. W. & Sahakian, B. J. Motor inhibition and cognitive flexibility in obsessive-compulsive disorder and trichotillomania. Am. J. Psychiatry 163, 1282\u20131284 (2006).","journal-title":"Am. J. Psychiatry"},{"key":"8729_CR15","doi-asserted-by":"publisher","first-page":"1225","DOI":"10.1001\/archpsyc.63.11.1225","volume":"63","author":"PL Remijnse","year":"2006","unstructured":"Remijnse, P. L. et al. Reduced orbitofrontal-striatal activity on a reversal learning task in obsessive-compulsive disorder. Arch. Gen. Psychiatry 63, 1225 (2006).","journal-title":"Arch. Gen. Psychiatry"},{"key":"8729_CR16","doi-asserted-by":"publisher","first-page":"1117","DOI":"10.1016\/j.biopsych.2011.01.008","volume":"69","author":"J Camchong","year":"2011","unstructured":"Camchong, J. et al. Frontal hyperconnectivity related to discounting and reversal learning in cocaine subjects. Biol. Psychiatry 69, 1117\u20131123 (2011).","journal-title":"Biol. Psychiatry"},{"key":"8729_CR17","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1093\/schbul\/sbn134","volume":"35","author":"JD Ragland","year":"2009","unstructured":"Ragland, J. D. et al. CNTRICS final task selection: long-term memory. Schizophr. Bull. 35, 197\u2013212 (2009).","journal-title":"Schizophr. Bull."},{"key":"8729_CR18","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1016\/j.neuroscience.2016.03.021","volume":"345","author":"A Izquierdo","year":"2017","unstructured":"Izquierdo, A., Brigman, J. L., Radke, A. K., Rudebeck, P. H. & Holmes, A. The neural basis of reversal learning: an updated perspective. Neuroscience 345, 12\u201326 (2017).","journal-title":"Neuroscience"},{"key":"8729_CR19","doi-asserted-by":"publisher","first-page":"3191","DOI":"10.1111\/bph.13826","volume":"174","author":"TW Robbins","year":"2017","unstructured":"Robbins, T. W. Cross-species studies of cognition relevant to drug discovery: a translational approach. Br. J. Pharmacol. 174, 3191\u20133199 (2017).","journal-title":"Br. J. Pharmacol."},{"key":"8729_CR20","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1017\/S0033291702007018","volume":"33","author":"FC Murphy","year":"2003","unstructured":"Murphy, F. C., Michael, A., Robbins, T. W. & Sahakian, B. J. Neuropsychological impairment in patients with major depressive disorder: the effects of feedback on task performance. Psychol. Med. 33, 455\u2013467 (2003).","journal-title":"Psychol. Med."},{"key":"8729_CR21","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1126\/science.1154433","volume":"321","author":"SR Chamberlain","year":"2008","unstructured":"Chamberlain, S. R. et al. Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives. Science (1979). 321, 421\u2013422 (2008).","journal-title":"Science"},{"key":"8729_CR22","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.conb.2010.01.007","volume":"20","author":"AA Kehagia","year":"2010","unstructured":"Kehagia, A. A., Murray, G. K. & Robbins, T. W. Learning and cognitive flexibility: frontostriatal function and monoaminergic modulation. Curr. Opin. Neurobiol. 20, 199\u2013204 (2010).","journal-title":"Curr. Opin. Neurobiol."},{"key":"8729_CR23","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1111\/psyp.12370","volume":"52","author":"GH Proudfit","year":"2015","unstructured":"Proudfit, G. H. The reward positivity: from basic research on reward to a biomarker for depression. Psychophysiology 52, 449\u2013459 (2015).","journal-title":"Psychophysiology"},{"key":"8729_CR24","doi-asserted-by":"publisher","first-page":"292","DOI":"10.3758\/s13415-023-01134-z","volume":"24","author":"P Kehrer","year":"2024","unstructured":"Kehrer, P., Brigman, J. L. & Cavanagh, J. F. Depth recordings of the mouse homologue of the reward positivity. Cogn. Affect Behav. Neurosci. 24, 292\u2013301 (2024).","journal-title":"Cogn. Affect Behav. Neurosci."},{"key":"8729_CR25","doi-asserted-by":"publisher","first-page":"788","DOI":"10.1162\/jocn.1997.9.6.788","volume":"9","author":"WHR Miltner","year":"1997","unstructured":"Miltner, W. H. R., Braun, C. H. & Coles, M. G. H. Event-related brain potentials following incorrect feedback in a time-estimation task: evidence for a \u201cgeneric\u201d neural system for error detection. J. Cogn. Neurosci. 9, 788\u2013798 (1997).","journal-title":"J. Cogn. Neurosci."},{"key":"8729_CR26","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1037\/0033-295X.109.4.679","volume":"109","author":"CB Holroyd","year":"2002","unstructured":"Holroyd, C. B. & Coles, M. G. H. The neural basis of human error processing: reinforcement learning, dopamine, and the error-related negativity. Psychol. Rev. 109, 679\u2013709 (2002).","journal-title":"Psychol. Rev."},{"key":"8729_CR27","doi-asserted-by":"publisher","first-page":"2561","DOI":"10.1097\/00001756-200411150-00027","volume":"15","author":"A Yasuda","year":"2004","unstructured":"Yasuda, A., Sato, A., Miyawaki, K., Kumano, H. & Kuboki, T. Error-related negativity reflects detection of negative reward prediction error. Neuroreport 15, 2561\u20132565 (2004).","journal-title":"Neuroreport"},{"key":"8729_CR28","doi-asserted-by":"publisher","first-page":"936","DOI":"10.1162\/jocn.2010.21456","volume":"23","author":"HW Chase","year":"2011","unstructured":"Chase, H. W., Swainson, R., Durham, L., Benham, L. & Cools, R. Feedback-related negativity codes prediction error but not behavioral adjustment during probabilistic reversal learning. J. Cogn. Neurosci. 23, 936\u2013946 (2011).","journal-title":"J. Cogn. Neurosci."},{"key":"8729_CR29","doi-asserted-by":"publisher","first-page":"688","DOI":"10.1111\/j.1469-8986.2008.00668.x","volume":"45","author":"CB Holroyd","year":"2008","unstructured":"Holroyd, C. B., Pakzad-Vaezi, K. L. & Krigolson, O. E. The feedback correct-related positivity: sensitivity of the event-related brain potential to unexpected positive feedback. Psychophysiology 45, 688\u2013697 (2008).","journal-title":"Psychophysiology"},{"key":"8729_CR30","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1097\/WNR.0b013e328345441d","volume":"22","author":"CB Holroyd","year":"2011","unstructured":"Holroyd, C. B., Krigolson, O. E. & Lee, S. Reward positivity elicited by predictive cues. Neuroreport 22, 249\u2013252 (2011).","journal-title":"Neuroreport"},{"key":"8729_CR31","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.neuroimage.2013.08.028","volume":"84","author":"TU Hauser","year":"2014","unstructured":"Hauser, T. U. et al. The feedback-related negativity (FRN) revisited: new insights into the localization, meaning and network organization. Neuroimage 84, 159\u2013168 (2014).","journal-title":"Neuroimage"},{"key":"8729_CR32","doi-asserted-by":"publisher","first-page":"e25591","DOI":"10.1371\/journal.pone.0025591","volume":"6","author":"TOJ Gruendler","year":"2011","unstructured":"Gruendler, T. O. J., Ullsperger, M. & Huster, R. J. Event-related potential correlates of performance-monitoring in a lateralized time-estimation task. PLoS ONE 6, e25591 (2011).","journal-title":"PLoS ONE"},{"key":"8729_CR33","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.neuron.2017.06.021","volume":"95","author":"JM Hyman","year":"2017","unstructured":"Hyman, J. M., Holroyd, C. B. & Seamans, J. K. A novel neural prediction error found in anterior cingulate cortex ensembles. Neuron 95, 447\u2013456.e3 (2017).","journal-title":"Neuron"},{"key":"8729_CR34","doi-asserted-by":"publisher","first-page":"1936","DOI":"10.1523\/JNEUROSCI.16-05-01936.1996","volume":"16","author":"P Montague","year":"1996","unstructured":"Montague, P., Dayan, P. & Sejnowski, T. A framework for mesencephalic dopamine systems based on predictive Hebbian learning.  J. Neurosci. 16, 1936\u20131947 (1996).","journal-title":"J. Neurosci."},{"key":"8729_CR35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1152\/jn.1998.80.1.1","volume":"80","author":"W Schultz","year":"1998","unstructured":"Schultz, W. Predictive reward signal of dopamine neurons. J. Neurophysiol. 80, 1\u201327 (1998).","journal-title":"J. Neurophysiol."},{"key":"8729_CR36","doi-asserted-by":"publisher","first-page":"129","DOI":"10.1016\/j.neuron.2005.05.020","volume":"47","author":"HM Bayer","year":"2005","unstructured":"Bayer, H. M. & Glimcher, P. W. Midbrain dopamine neurons encode a quantitative reward prediction error signal. Neuron 47, 129\u2013141 (2005).","journal-title":"Neuron"},{"key":"8729_CR37","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1126\/science.1105783","volume":"307","author":"JW Brown","year":"2005","unstructured":"Brown, J. W. & Braver, T. S. Learned predictions of error likelihood in the anterior cingulate cortex. Science 307, 1118\u20131121 (2005).","journal-title":"Science"},{"key":"8729_CR38","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1523\/JNEUROSCI.4421-06.2007","volume":"27","author":"MX Cohen","year":"2007","unstructured":"Cohen, M. X. & Ranganath, C. Reinforcement learning signals predict future decisions.  J. Neurosci. 27, 371\u2013378 (2007).","journal-title":"J. Neurosci."},{"key":"8729_CR39","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01562-w","volume":"11","author":"JF Cavanagh","year":"2021","unstructured":"Cavanagh, J. F. et al. Electrophysiological biomarkers of behavioral dimensions from cross-species paradigms. Transl. Psychiatry 11, 482 (2021).","journal-title":"Transl. Psychiatry"},{"key":"8729_CR40","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1038\/npp.2009.233","volume":"35","author":"A Bari","year":"2010","unstructured":"Bari, A. et al. Serotonin modulates sensitivity to reward and negative feedback in a probabilistic reversal learning task in rats. Neuropsychopharmacology 35, 1290\u20131301 (2010).","journal-title":"Neuropsychopharmacology"},{"key":"8729_CR41","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.1038\/s41386-022-01514-y","volume":"48","author":"MM Tranter","year":"2023","unstructured":"Tranter, M. M., Aggarwal, S., Young, J. W., Dillon, D. G. & Barnes, S. A. Reinforcement learning deficits exhibited by postnatal PCP-treated rats enable deep neural network classification. Neuropsychopharmacology 48, 1377\u20131385 (2023).","journal-title":"Neuropsychopharmacology"},{"key":"8729_CR42","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1007\/s00213-022-06082-z","volume":"239","author":"JF Cavanagh","year":"2022","unstructured":"Cavanagh, J. F. et al. Amphetamine alters an EEG marker of reward processing in humans and mice. Psychopharmacology 239, 923\u2013933 (2022).","journal-title":"Psychopharmacology"},{"key":"8729_CR43","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1001\/jama.2009.351","volume":"301","author":"ND Volkow","year":"2009","unstructured":"Volkow, N. D. et al. Effects of modafinil on dopamine and dopamine transporters in the male human brain. JAMA 301, 1148 (2009).","journal-title":"JAMA"},{"key":"8729_CR44","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1016\/j.bpsgos.2023.08.002","volume":"4","author":"MM Tranter","year":"2024","unstructured":"Tranter, M. M. et al. Postnatal phencyclidine-induced deficits in decision making are ameliorated by optogenetic inhibition of ventromedial orbitofrontal cortical glutamate neurons. Biol. Psychiatry Glob. Open Sci. 4, 264\u2013274 (2024).","journal-title":"Biol. Psychiatry Glob. Open Sci."},{"key":"8729_CR45","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1098\/rstb.2007.2098","volume":"362","author":"JD Cohen","year":"2007","unstructured":"Cohen, J. D., McClure, S. M. & Yu, A. J. Should I stay or should I go? How the human brain manages the trade-off between exploitation and exploration. Philos. Trans. R. Soc. B Biol. Sci. 362, 933\u2013942 (2007).","journal-title":"Philos. Trans. R. Soc. B Biol. Sci."},{"key":"8729_CR46","doi-asserted-by":"publisher","first-page":"1593","DOI":"10.1126\/science.275.5306.1593","volume":"275","author":"W Schultz","year":"1997","unstructured":"Schultz, W., Dayan, P. & Montague, P. R. A neural substrate of prediction and reward. Science (1979). 275, 1593\u20131599 (1997).","journal-title":"Science"},{"key":"8729_CR47","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.conb.2006.03.006","volume":"16","author":"ND Daw","year":"2006","unstructured":"Daw, N. D. & Doya, K. The computational neurobiology of learning and reward. Curr. Opin. Neurobiol. 16, 199\u2013204 (2006).","journal-title":"Curr. Opin. Neurobiol."},{"key":"8729_CR48","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1111\/j.1476-5381.2009.00267.x","volume":"157","author":"V Sharma","year":"2009","unstructured":"Sharma, V. & McNeill, J. H. To scale or not to scale: the principles of dose extrapolation. Br. J. Pharmacol. 157, 907\u2013921 (2009).","journal-title":"Br. J. Pharmacol."},{"key":"8729_CR49","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1037\/bul0000006","volume":"141","author":"TD Sambrook","year":"2015","unstructured":"Sambrook, T. D. & Goslin, J. A neural reward prediction error revealed by a meta-analysis of ERPs using great grand averages. Psychol. Bull. 141, 213\u2013235 (2015).","journal-title":"Psychol. Bull."},{"key":"8729_CR50","doi-asserted-by":"publisher","first-page":"613","DOI":"10.1007\/s00213-016-4497-1","volume":"234","author":"M Rychlik","year":"2017","unstructured":"Rychlik, M., Bollen, E. & Rygula, R. Ketamine decreases sensitivity of male rats to misleading negative feedback in a probabilistic reversal-learning task. Psychopharmacology 234, 613\u2013620 (2017).","journal-title":"Psychopharmacology"},{"key":"8729_CR51","doi-asserted-by":"publisher","first-page":"5783","DOI":"10.1093\/cercor\/bhac459","volume":"33","author":"SA Barnes","year":"2023","unstructured":"Barnes, S. A. et al. Modulation of ventromedial orbitofrontal cortical glutamatergic activity affects the explore-exploit balance and influences value-based decision-making. Cereb. Cortex 33, 5783\u20135796 (2023).","journal-title":"Cereb. Cortex"},{"key":"8729_CR52","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1038\/s41386-021-01188-y","volume":"47","author":"SJ Millard","year":"2022","unstructured":"Millard, S. J., Bearden, C. E., Karlsgodt, K. H. & Sharpe, M. J. The prediction-error hypothesis of schizophrenia: new data point to circuit-specific changes in dopamine activity. Neuropsychopharmacology 47, 628\u2013640 (2022).","journal-title":"Neuropsychopharmacology"},{"key":"8729_CR53","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.jphysparis.2014.08.008","volume":"109","author":"CM Warren","year":"2015","unstructured":"Warren, C. M., Hyman, J. M., Seamans, J. K. & Holroyd, C. B. Feedback-related negativity observed in rodent anterior cingulate cortex. J. Physiol. Paris 109, 87\u201394 (2015).","journal-title":"J. Physiol. Paris"},{"key":"8729_CR54","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1016\/j.bpsgos.2022.08.005","volume":"3","author":"MK Young","year":"2023","unstructured":"Young, M. K. et al. Activity in the dorsomedial striatum underlies serial reversal learning performance under probabilistic uncertainty. Biol. Psychiatry Glob. Open Sci. 3, 1030\u20131041 (2023).","journal-title":"Biol. Psychiatry Glob. Open Sci."},{"key":"8729_CR55","doi-asserted-by":"publisher","first-page":"1477","DOI":"10.1038\/sj.npp.1301534","volume":"33","author":"MJ Minzenberg","year":"2008","unstructured":"Minzenberg, M. J. & Carter, C. S. Modafinil: a review of neurochemical actions and effects on cognition. Neuropsychopharmacology 33, 1477\u20131502 (2008).","journal-title":"Neuropsychopharmacology"},{"key":"8729_CR56","doi-asserted-by":"publisher","first-page":"256","DOI":"10.1016\/j.biopsych.2024.01.025","volume":"96","author":"A Basu","year":"2024","unstructured":"Basu, A. et al. Frontal norepinephrine represents a threat prediction error under uncertainty. Biol. Psychiatry 96, 256\u2013267 (2024).","journal-title":"Biol. Psychiatry"},{"key":"8729_CR57","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1038\/s41386-023-01762-6","volume":"49","author":"Q Luo","year":"2024","unstructured":"Luo, Q. et al. Comparable roles for serotonin in rats and humans for computations underlying flexible decision-making. Neuropsychopharmacology 49, 600\u2013608 (2024).","journal-title":"Neuropsychopharmacology"},{"key":"8729_CR58","doi-asserted-by":"publisher","first-page":"4370","DOI":"10.1523\/JNEUROSCI.4437-04.2005","volume":"25","author":"J Riba","year":"2005","unstructured":"Riba, J., Rodr\u00edguez-Fornells, A., Morte, A., M\u00fcnte, T. F. & Barbanoj, M. J. Noradrenergic stimulation enhances human action monitoring.  J. Neurosci. 25, 4370\u20134374 (2005).","journal-title":"J. Neurosci."},{"key":"8729_CR59","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1007\/7854_2015_5004","volume":"28","author":"A Der-Avakian","year":"2015","unstructured":"Der-Avakian, A., Barnes, S. A., Markou, A. & Pizzagalli, D. A. Translational assessment of reward and motivational deficits in psychiatric disorders. Curr. Top. Behav. Neurosci. 28, 231\u2013262 (2015).","journal-title":"Curr. Top. Behav. Neurosci."},{"key":"8729_CR60","unstructured":"First, M. B., Williams, J. B. W., Karg, R. S. & Spitzer, R. L. Structured clinical interview for DSM-5 \u2014 research version (SCID-5 for DSM-5, Research Version; SCID-5-RV). (Arlington, VA, American Psychiatric Association, 2015)."},{"key":"8729_CR61","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1038\/s41386-021-00998-4","volume":"46","author":"MA Robble","year":"2021","unstructured":"Robble, M. A. et al. Concordant neurophysiological signatures of cognitive control in humans and rats. Neuropsychopharmacology 46, 1252\u20131262 (2021).","journal-title":"Neuropsychopharmacology"},{"key":"8729_CR62","doi-asserted-by":"publisher","first-page":"770","DOI":"10.1038\/nrn3599","volume":"14","author":"GT Einevoll","year":"2013","unstructured":"Einevoll, G. T., Kayser, C., Logothetis, N. K. & Panzeri, S. Modelling and analysis of local field potentials for studying the function of cortical circuits. Nat. Rev. Neurosci. 14, 770\u2013785 (2013).","journal-title":"Nat. Rev. Neurosci."},{"key":"8729_CR63","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1038\/nrn3241","volume":"13","author":"G Buzs\u00e1ki","year":"2012","unstructured":"Buzs\u00e1ki, G., Anastassiou, C. A. & Koch, C. The origin of extracellular fields and currents \u2014 EEG, ECoG, LFP and spikes. Nat. Rev. Neurosci. 13, 407\u2013420 (2012).","journal-title":"Nat. Rev. Neurosci."}],"container-title":["Communications Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08729-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08729-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08729-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T14:00:37Z","timestamp":1757426437000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s42003-025-08729-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,23]]},"references-count":63,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["8729"],"URL":"https:\/\/doi.org\/10.1038\/s42003-025-08729-x","relation":{},"ISSN":["2399-3642"],"issn-type":[{"value":"2399-3642","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,23]]},"assertion":[{"value":"18 June 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 August 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 August 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Over the past 3 years, B.D.K. has had sponsored research agreements with BlackThorn Therapeutics, Compass Pathways, Delix Therapeutics, Engrail Therapeutics, Neurocrine Biosciences, and Takeda Pharmaceuticals. Over the past 3 years, V.B.R. has received consulting fees from Engrail Pharmaceuticals, Jazz Pharmaceuticals, and Cohen Veterans Biosciences. Over the past 3 years, D.A.P. has received consulting fees from Arrowhead Pharmaceuticals, Boehringer Ingelheim, Compass Pathways, Engrail Therapeutics, Neumora Therapeutics, Neurocrine Biosciences, Neuroscience Software, and Takeda; he has received honoraria from the American Psychological Society, Psychonomic Society and Springer (for editorial work) and from Alkermes; he has received research funding from the Bird Foundation, Brain and Behavior Research Foundation, Dana Foundation, DARPA, Millennium Pharmaceuticals, the National Institute of Mental Health, and Wellcome Leap; he has received stock options from Ceretype Neuromedicine, Compass Pathways, Engrail Therapeutics, Neumora Therapeutics, and Neuroscience Software. No funding or any involvement from these entities was used to support the current work, and all views expressed are solely those of the authors. All other authors have no conflicts of interest or relevant disclosures.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1268"}}