reversal learning


Summary: Any situation where an animal or human is trained to respond differentially to two stimuli (e.g., approach and avoidance) under reward and punishment conditions and subsequently trained under reversed reward values (i.e., the approach which was previously rewarded is punished and vice versa).

Top Publications

  1. Kay C, Harper D, Hunt M. The effects of binge MDMA on acquisition and reversal learning in a radial-arm maze task. Neurobiol Learn Mem. 2011;95:473-83 pubmed publisher
  2. Chamberlain S, Menzies L, Hampshire A, Suckling J, Fineberg N, Del Campo N, et al. Orbitofrontal dysfunction in patients with obsessive-compulsive disorder and their unaffected relatives. Science. 2008;321:421-2 pubmed publisher
    ..the orbitofrontal cortex, a neural region that facilitates behavioral flexibility after negative feedback (reversal learning)...
  3. Rodriguez J, Zürcher N, KEENAN K, Bartlett T, Nathanielsz P, Nijland M. Prenatal betamethasone exposure has sex specific effects in reversal learning and attention in juvenile baboons. Am J Obstet Gynecol. 2011;204:545.e1-10 pubmed publisher
    ..In summary, behavioral effects observed show sex-specific differences in resilience to multiple fetal ?M exposures. ..
  4. Wu Y, Ren Q, Li H, Guo A. The GABAergic anterior paired lateral neurons facilitate olfactory reversal learning in Drosophila. Learn Mem. 2012;19:478-86 pubmed publisher
    b>Reversal learning has been widely used to probe the implementation of cognitive flexibility in the brain. Previous studies in monkeys identified an essential role of the orbitofrontal cortex (OFC) in reversal learning...
  5. Amodeo D, Jones J, Sweeney J, Ragozzino M. Differences in BTBR T+ tf/J and C57BL/6J mice on probabilistic reversal learning and stereotyped behaviors. Behav Brain Res. 2012;227:64-72 pubmed publisher
    ..The present experiment investigated performance of BTBR T+ tf/J and C57BL/6J on two different spatial reversal learning tests (100% accurate feedback and 80/20 probabilistic feedback), as well as marble burying and grooming ..
  6. Adleman N, Kayser R, DICKSTEIN D, Blair R, Pine D, Leibenluft E. Neural correlates of reversal learning in severe mood dysregulation and pediatric bipolar disorder. J Am Acad Child Adolesc Psychiatry. 2011;50:1173-1185.e2 pubmed publisher
    ..In response to errors, similar perturbations occur in the caudate for youth with SMD and BD compared with HV youth. IFG deficits, in contrast, manifest in youth with SMD, but not with BD. ..
  7. Bissonette G, Powell E. Reversal learning and attentional set-shifting in mice. Neuropharmacology. 2012;62:1168-74 pubmed publisher
    ..This review highlights the most recent developments from behavioral paradigms for testing orbital and medial prefrontal cortical function in pharmacological and genetic models of human schizophrenia. ..
  8. Rutten K, Wallace T, Works M, Prickaerts J, Blokland A, Novak T, et al. Enhanced long-term depression and impaired reversal learning in phosphodiesterase 4B-knockout (PDE4B-/-) mice. Neuropharmacology. 2011;61:138-47 pubmed publisher
    ..On the behavioral level PDE4B(-/-) mice displayed impaired reversal learning in the Morris water maze compared to wild-type littermates, but no differences in acquisition and retention ..
  9. Levy Gigi E, Kelemen O, Gluck M, Keri S. Impaired context reversal learning, but not cue reversal learning, in patients with amnestic mild cognitive impairment. Neuropsychologia. 2011;49:3320-6 pubmed publisher
    It has been proposed that reversal learning is impaired following damage to the orbitofrontal and ventromedial frontal cortex (OFC/VMFC) and to the medial temporal lobe (MTL), including the hippocampal formation...

Scientific Experts

More Information


  1. Mizoguchi K, Shoji H, Tanaka Y, Tabira T. Orbitofrontal dopaminergic dysfunction causes age-related impairment of reversal learning in rats. Neuroscience. 2010;170:1110-9 pubmed publisher
    b>Reversal learning is a domain that involves cognitive flexibility and is defined as the ability to rapidly alter established patterns of behavior when confronted with changing circumstances...
  2. Clarke H, Robbins T, Roberts A. Lesions of the medial striatum in monkeys produce perseverative impairments during reversal learning similar to those produced by lesions of the orbitofrontal cortex. J Neurosci. 2008;28:10972-82 pubmed publisher
  3. Izquierdo A, Jentsch J. Reversal learning as a measure of impulsive and compulsive behavior in addictions. Psychopharmacology (Berl). 2012;219:607-20 pubmed publisher
    ..One task in particular, reversal learning, has proven valuable in assessing the inhibitory processes that are central to executive control...
  4. Labrie V, Duffy S, Wang W, Barger S, Baker G, Roder J. Genetic inactivation of D-amino acid oxidase enhances extinction and reversal learning in mice. Learn Mem. 2009;16:28-37 pubmed publisher
    ..The NMDAR glycine site and DAO may be promising therapeutic targets to improve cognitive flexibility and inhibitory learning in psychiatric disorders such as schizophrenia and anxiety syndromes. ..
  5. De Steno D, Schmauss C. A role for dopamine D2 receptors in reversal learning. Neuroscience. 2009;162:118-27 pubmed publisher
    b>Reversal learning has been shown to require intact serotonergic innervation of the forebrain neocortex. Whether dopamine acting through D2 receptors plays a complementary role in this anatomic area is still unclear...
  6. Parker M, Gaviria J, Haigh A, Millington M, Brown V, Combe F, et al. Discrimination reversal and attentional sets in zebrafish (Danio rerio). Behav Brain Res. 2012;232:264-8 pubmed publisher
    ..b>Reversal learning deficits have been implicated in a variety of human psychological disorders (e.g...
  7. Harte L, Dow Edwards D. Sexually dimorphic alterations in locomotion and reversal learning after adolescent tetrahydrocannabinol exposure in the rat. Neurotoxicol Teratol. 2010;32:515-24 pubmed publisher
  8. Shirey J, Brady A, Jones P, Davis A, Bridges T, Kennedy J, et al. A selective allosteric potentiator of the M1 muscarinic acetylcholine receptor increases activity of medial prefrontal cortical neurons and restores impairments in reversal learning. J Neurosci. 2009;29:14271-86 pubmed publisher
    ..BQCA also restored discrimination reversal learning in a transgenic mouse model of Alzheimer's disease and was found to regulate non-amyloidogenic APP ..
  9. Mendez M, Mendez Lopez M, Lopez L, Aller M, Arias J, Arias J. Portosystemic hepatic encephalopathy model shows reversal learning impairment and dysfunction of neural activity in the prefrontal cortex and regions involved in motivated behavior. J Clin Neurosci. 2011;18:690-4 pubmed publisher
    ..In order to investigate learning impairment and brain functional alterations in this model, we assessed reversal learning and neural metabolic activity in a PCS rat model...
  10. Freyer T, Valerius G, Kuelz A, Speck O, Glauche V, Hull M, et al. Test-retest reliability of event-related functional MRI in a probabilistic reversal learning task. Psychiatry Res. 2009;174:40-6 pubmed publisher
    ..10 healthy adult subjects were scanned in two sessions, 16 weeks apart, while performing a probabilistic reversal learning task known to activate orbitofrontal-striatal circuitry...
  11. Leenaars C, Joosten R, Kramer M, Post G, Eggels L, Wuite M, et al. Spatial reversal learning is robust to total sleep deprivation. Behav Brain Res. 2012;230:40-7 pubmed publisher
    ..We first evaluated the effect of sleep deprivation on the acquisition of reversal learning. Performance on reversal learning after 12h of sleep deprivation (n=12) was compared to performance after ..
  12. Murray G, Cheng F, Clark L, Barnett J, Blackwell A, Fletcher P, et al. Reinforcement and reversal learning in first-episode psychosis. Schizophr Bull. 2008;34:848-55 pubmed publisher
    Abnormalities in reinforcement learning and reversal learning have been reported in psychosis, possibly secondary to subcortical dopamine abnormalities...
  13. Wilson C, Gaffan D. Prefrontal-inferotemporal interaction is not always necessary for reversal learning. J Neurosci. 2008;28:5529-38 pubmed publisher more posterior regions of cortex in a "top-down" manner, a function thought to be tested by reversal learning tasks...
  14. Finger E, Marsh A, Mitchell D, Reid M, Sims C, Budhani S, et al. Abnormal ventromedial prefrontal cortex function in children with psychopathic traits during reversal learning. Arch Gen Psychiatry. 2008;65:586-94 pubmed publisher
    ..traits and conduct or oppositional defiant disorder demonstrate poor decision making and are impaired in reversal learning. However, the neural basis of this impairment has not previously been investigated...
  15. Dickstein D, Finger E, Brotman M, Rich B, Pine D, Blair J, et al. Impaired probabilistic reversal learning in youths with mood and anxiety disorders. Psychol Med. 2010;40:1089-100 pubmed publisher
    ..b>Reversal learning is one such process, whereby subjects must first acquire stimulus/reward and stimulus/punishment ..
  16. South M, Newton T, Chamberlain P. Delayed reversal learning and association with repetitive behavior in autism spectrum disorders. Autism Res. 2012;5:398-406 pubmed publisher
    ..and adolescents diagnosed with ASD and 29 age- and intelligence quotient-matched controls completed a reversal learning paradigm following partial reinforcement Pavlovian fear conditioning, using a surprising air puff as the ..
  17. van der Schaaf M, Fallon S, ter Huurne N, Buitelaar J, Cools R. Working memory capacity predicts effects of methylphenidate on reversal learning. Neuropsychopharmacology. 2013;38:2011-8 pubmed publisher
    ..Moreover, they highlight the importance of taking into account both inter- and intra-individual differences in dopaminergic drug research. ..
  18. McCracken C, Grace A. Persistent cocaine-induced reversal learning deficits are associated with altered limbic cortico-striatal local field potential synchronization. J Neurosci. 2013;33:17469-82 pubmed publisher
    ..Animals were then tested on a cross-maze-based reversal learning and set-shifting task, after which they were anesthetized to allow for recording of spontaneous local field ..
  19. Stack C, Lim M, Cuasay K, Stone M, Seibert K, Spivak Pohis I, et al. Deficits in social behavior and reversal learning are more prevalent in male offspring of VIP deficient female mice. Exp Neurol. 2008;211:67-84 pubmed publisher
    ..all male offspring of VIP deficient mothers exhibited severe deficits in social approach behavior and reversal learning. The deficits in these behaviors in the female offspring of VIP deficient mothers were less severe than in ..
  20. Brushfield A, Luu T, Callahan B, Gilbert P. A comparison of discrimination and reversal learning for olfactory and visual stimuli in aged rats. Behav Neurosci. 2008;122:54-62 pubmed publisher
    The present study investigated age-related differences in discrimination and reversal learning for olfactory and visual stimuli in 6-month and 24-month-old rats...
  21. Nilsson S, Ripley T, Somerville E, Clifton P. Reduced activity at the 5-HT(2C) receptor enhances reversal learning by decreasing the influence of previously non-rewarded associations. Psychopharmacology (Berl). 2012;224:241-54 pubmed publisher
    b>Reversal learning deficits are a feature of many human psychopathologies and their associated animal models and have recently been shown to involve the 5-HT(2C) receptor (5-HT(2C)R)...
  22. Raine N, Chittka L. No trade-off between learning speed and associative flexibility in bumblebees: a reversal learning test with multiple colonies. PLoS ONE. 2012;7:e45096 pubmed publisher
    ..Here, we test whether rapid learning interferes with the acquisition of new information using a reversal learning paradigm. Bumblebees (Bombus terrestris) were trained to associate yellow with a floral reward...
  23. Kalm M, Karlsson N, Nilsson M, Blomgren K. Loss of hippocampal neurogenesis, increased novelty-induced activity, decreased home cage activity, and impaired reversal learning one year after irradiation of the young mouse brain. Exp Neurol. 2013;247:402-9 pubmed publisher
    ..Place learning in the IntelliCage was unaffected by irradiation but reversal learning was impaired...
  24. Bellebaum C, Koch B, Schwarz M, Daum I. Focal basal ganglia lesions are associated with impairments in reward-based reversal learning. Brain. 2008;131:829-41 pubmed publisher
    ..On the group level, BG patients showed deficits in reversal learning, with dorsal striatum lesion patients being most severely affected...
  25. Clarke H, Hill G, Robbins T, Roberts A. Dopamine, but not serotonin, regulates reversal learning in the marmoset caudate nucleus. J Neurosci. 2011;31:4290-7 pubmed publisher
    Studies of visual discrimination reversal learning have revealed striking neurochemical dissociations at the level of the orbitofrontal cortex (OFC) with serotoninergic, but not dopaminergic, integrity being important for successful ..
  26. den Ouden H, Daw N, Fernandez G, Elshout J, Rijpkema M, Hoogman M, et al. Dissociable effects of dopamine and serotonin on reversal learning. Neuron. 2013;80:1090-100 pubmed publisher
    ..We studied the role of these neurotransmitters in probabilistic reversal learning in nearly 700 individuals as a function of two polymorphisms in the genes encoding the serotonin and ..
  27. Boulougouris V, Castañé A, Robbins T. Dopamine D2/D3 receptor agonist quinpirole impairs spatial reversal learning in rats: investigation of D3 receptor involvement in persistent behavior. Psychopharmacology (Berl). 2009;202:611-20 pubmed publisher
    ..1 mg/kg) or nafadotride (1.0 mg/kg) with quinpirole (0.3 mg/kg) on spatial discrimination and reversal learning. Rats were trained on an instrumental two-lever spatial discrimination and reversal learning task...
  28. Watson D, Stanton M. Intrahippocampal administration of an NMDA-receptor antagonist impairs spatial discrimination reversal learning in weanling rats. Neurobiol Learn Mem. 2009;92:89-98 pubmed publisher
    Systemic administration of MK-801, an NMDA-receptor antagonist, impairs reversal learning in weanling rats [Chadman, K.K., Watson, D.J., & Stanton, M.E. (2006). NMDA-receptor antagonism impairs reversal learning in developing rats...
  29. Boulougouris V, Robbins T. Enhancement of spatial reversal learning by 5-HT2C receptor antagonism is neuroanatomically specific. J Neurosci. 2010;30:930-8 pubmed publisher
    ..administration of 5-HT(2C) and 5-HT(2A) receptor antagonists significantly enhanced and impaired spatial reversal learning, respectively...
  30. D Cruz A, Ragozzino M, Mosconi M, Pavuluri M, Sweeney J. Human reversal learning under conditions of certain versus uncertain outcomes. Neuroimage. 2011;56:315-22 pubmed publisher
    b>Reversal learning tasks assess behavioral flexibility by requiring subjects to switch from one learned response choice to a different response choice when task contingencies change...
  31. Floresco S, Zhang Y, Enomoto T. Neural circuits subserving behavioral flexibility and their relevance to schizophrenia. Behav Brain Res. 2009;204:396-409 pubmed publisher
    Impairments in different forms of behavioral flexibility, such as set-shifting and reversal learning, are some of the most reliable cognitive deficits associated with schizophrenia, and have been attributed to a disruption in frontal ..
  32. Wei C, Singer P, Coelho J, Boison D, Feldon J, Yee B, et al. Selective inactivation of adenosine A(2A) receptors in striatal neurons enhances working memory and reversal learning. Learn Mem. 2011;18:459-74 pubmed publisher
    ..KO) or to striatum alone (st-A(2A)R KO) in recognition memory, working memory, reference memory, and reversal learning. This comprehensive, comparative analysis showed for the first time that depletion of A(2A)R-dependent ..
  33. Sanders D, Kanazono S, Wininger F, Whiting R, Flournoy C, Coates J, et al. A reversal learning task detects cognitive deficits in a Dachshund model of late-infantile neuronal ceroid lipofuscinosis. Genes Brain Behav. 2011;10:798-804 pubmed publisher
    ..Cognitive function was assessed using a T-maze reversal learning (RL) task...
  34. Clatworthy P, Lewis S, Brichard L, Hong Y, Izquierdo D, Clark L, et al. Dopamine release in dissociable striatal subregions predicts the different effects of oral methylphenidate on reversal learning and spatial working memory. J Neurosci. 2009;29:4690-6 pubmed publisher
    ..Methylphenidate produced significantly different effects on reversal learning and spatial working memory tasks within individuals...
  35. McLean S, Woolley M, Thomas D, Neill J. Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat. Psychopharmacology (Berl). 2009;206:403-14 pubmed publisher
    ..was to investigate the involvement of 5-HT receptor mechanisms in sub-chronic phencyclidine (PCP)-induced reversal learning deficits in female rats, a task of relevance to schizophrenia...
  36. Potter G, McQuoid D, Payne M, Taylor W, Steffens D. Association of attentional shift and reversal learning to functional deficits in geriatric depression. Int J Geriatr Psychiatry. 2012;27:1172-9 pubmed publisher depressed older adults and two types of executive function processes, attentional set shifting and reversal learning. Participants (N = 89) were aged 60 or over and enrolled in a naturalistic treatment study of major ..
  37. Hampshire A, Chaudhry A, Owen A, Roberts A. Dissociable roles for lateral orbitofrontal cortex and lateral prefrontal cortex during preference driven reversal learning. Neuroimage. 2012;59:4102-12 pubmed publisher
    One of the archetypal task manipulations known to depend on frontal-lobe function is reversal learning, where a dominant response must be overridden due to changes in the contingencies relating stimuli, responses, and environmental ..
  38. Camchong J, MacDonald A, Nelson B, Bell C, Mueller B, SPECKER S, et al. Frontal hyperconnectivity related to discounting and reversal learning in cocaine subjects. Biol Psychiatry. 2011;69:1117-23 pubmed publisher
    ..we hypothesized that abnormalities would be associated with poor performance in delayed discounting and reversal learning tasks...
  39. Graybeal C, Feyder M, Schulman E, Saksida L, Bussey T, Brigman J, et al. Paradoxical reversal learning enhancement by stress or prefrontal cortical damage: rescue with BDNF. Nat Neurosci. 2011;14:1507-9 pubmed publisher
    Stress affects various forms of cognition. We found that moderate stress enhanced late reversal learning in a mouse touchscreen-based choice task...
  40. Arnall S, Cheam L, Smart C, Rengel A, Fitzgerald M, Thivierge J, et al. Abnormal strategies during visual discrimination reversal learning in ephrin-A2(-/-) mice. Behav Brain Res. 2010;209:109-13 pubmed publisher
    ..However, during reversal learning, when the rewarded stimulus was switched, the two genotypes exhibited differences in response strategies: ..
  41. Han X, Wang W, Xue X, Shao F, Li N. Brief social isolation in early adolescence affects reversal learning and forebrain BDNF expression in adult rats. Brain Res Bull. 2011;86:173-8 pubmed publisher
    ..We found that early isolation rearing affected reversal learning without interfering with spatial learning in the Morris water maze...
  42. Ohira H, Matsunaga M, Kimura K, Murakami H, Osumi T, Isowa T, et al. Chronic stress modulates neural and cardiovascular responses during reversal learning. Neuroscience. 2011;193:193-204 pubmed publisher
    ..Twenty healthy men exposed to low or high chronic job stress performed a stochastic reversal learning task, which required cognitive flexibility and the goal-directed action...
  43. Knapman A, Heinzmann J, Holsboer F, Landgraf R, Touma C. Modeling psychotic and cognitive symptoms of affective disorders: Disrupted latent inhibition and reversal learning deficits in highly stress reactive mice. Neurobiol Learn Mem. 2010;94:145-52 pubmed publisher
    ..Male mice from these three breeding lines were subjected to a reversal learning task and latent inhibition (Li) was assessed using a conditioned taste aversion paradigm...
  44. Laughlin R, Grant T, Williams R, Jentsch J. Genetic dissection of behavioral flexibility: reversal learning in mice. Biol Psychiatry. 2011;69:1109-16 pubmed publisher
    ..Here, we investigate the genetic basis of individual differences in flexibility, measured using an operant reversal learning task...
  45. Idris N, Neill J, Grayson B, Bang Andersen B, Witten L, Brennum L, et al. Sertindole improves sub-chronic PCP-induced reversal learning and episodic memory deficits in rodents: involvement of 5-HT(6) and 5-HT (2A) receptor mechanisms. Psychopharmacology (Berl). 2010;208:23-36 pubmed publisher
    ..In the first test, adult female hooded Lister rats were trained to perform an operant reversal learning task to 90% criterion. After training, rats were treated with PCP at 2 mg/kg (i.p...
  46. Chase H, 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. 2011;23:936-46 pubmed publisher
    ..over the medial frontal cortex (MFC) during outcome-based behavioral adjustment using a probabilistic reversal learning task...
  47. McKirdy J, Sussmann J, Hall J, Lawrie S, Johnstone E, McIntosh A. Set shifting and reversal learning in patients with bipolar disorder or schizophrenia. Psychol Med. 2009;39:1289-93 pubmed publisher
    ..Deficits in reversal learning (RL) have also been shown in schizophrenia but not in bipolar disorder...
  48. Floresco S, Block A, Tse M. Inactivation of the medial prefrontal cortex of the rat impairs strategy set-shifting, but not reversal learning, using a novel, automated procedure. Behav Brain Res. 2008;190:85-96 pubmed publisher
    ..In the present study, we assessed the effects of inactivation of the mPFC on strategy set-shifting and reversal learning, using a novel, automated procedure conducted in an operant chamber...
  49. Peterson D, Elliott C, Song D, Makeig S, Sejnowski T, Poizner H. Probabilistic reversal learning is impaired in Parkinson's disease. Neuroscience. 2009;163:1092-101 pubmed publisher
    ..Nat Neurosci 9:1057-1063] for use as a reversal learning task with humans...
  50. Dong Z, Bai Y, Wu X, Li H, Gong B, Howland J, et al. Hippocampal long-term depression mediates spatial reversal learning in the Morris water maze. Neuropharmacology. 2013;64:65-73 pubmed publisher
    ..administration of these two mechanistically and structurally distinct inhibitors impaired spatial reversal learning of a novel target location, when the hidden platform was moved to the quadrant opposite the initial target ..
  51. Fidalgo C, Conejo N, Gonzalez Pardo H, Arias J. Cortico-limbic-striatal contribution after response and reversal learning: a metabolic mapping study. Brain Res. 2011;1368:143-50 pubmed publisher
    ..Particular subdivisions of the striatum have been shown to be critical for both motor-response learning and reversal learning. However, recent evidence suggests that different cortical and subcortical brain regions may be involved in ..
  52. Lapiz Bluhm M, Soto Piña A, Hensler J, Morilak D. Chronic intermittent cold stress and serotonin depletion induce deficits of reversal learning in an attentional set-shifting test in rats. Psychopharmacology (Berl). 2009;202:329-41 pubmed publisher
    ..Orbitofrontal cortex (OFC) has been implicated specifically in reversal learning, a form of cognitive flexibility modulated by 5-HT...
  53. Fortier C, Steffen E, LaFleche G, Venne J, Disterhoft J, McGlinchey R. Delay discrimination and reversal eyeblink classical conditioning in abstinent chronic alcoholics. Neuropsychology. 2008;22:196-208 pubmed publisher
    ..It is suggested that a factor important to alcoholic addiction may be the presence of alcoholic-related associative responses that interfere with the ability to learn new more adaptive associations. ..