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The neural basis of reversal learning: An updated perspective
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Reversal learning paradigms are among the most widely used tests of cognitive flexibility and have been used as assays, across species, for altered cognitive processes in a host of neuropsychiatric conditions. Based on recent studies in humans, non-human primates, and rodents, the notion that reversal learning tasks primarily measure response inhibition, has been revised. In this review, we describe how cognitive flexibility is measured by reversal learning and discuss new definitions of the construct validity of the task that are serving as a heuristic to guide future research in this field. We also provide an update on the available evidence implicating certain cortical and subcortical brain regions in the mediation of reversal learning, and an overview of the principal neurotransmitter systems involved.
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“PRL performance depends on complex interactions between several component processes, including the sensitivity to positive and negative feedback, response persistence and exploration versus exploitation, each of which requires functional activity in distinct PFC regions (Verharen et al., 2018(Verharen et al., , 2020)), as well as brain regions outside the PFC (Izquierdo et al., 2017).”
From Social Play Behavior Is Critical for the Development of Prefrontal Inhibitory Synapses and Cognitive Flexibility in Rats (2022) · cites this paper as Izquierdo et al., 2017
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“Extensive research in rodents and non-human primates emphasises the major roles of fronto-striatal circuits in the ability to respond flexibly [34–42].”
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“These paradigms assess the ability to respond adaptively in the face of changing stimulus–outcome or response–outcome contingencies15.”
From Cognitive and behavioural flexibility: Neural mechanisms and clinical considerations (2021) · cites this paper as [15]
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“OFC inactivation in rats impairs reversal learning owing to perseverance of previously learned choices15.”
From Cognitive and behavioural flexibility: Neural mechanisms and clinical considerations (2021) · cites this paper as [15]
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“To study cognitive flexibility in both humans and animals, reversal learning paradigms are often used.19, 20”
From Behavioral flexibility in a mouse model for obsessive‐compulsive disorder: Impaired Pavlovian reversal learning in SAPAP3 mutants (2019) · cites this paper as [19]
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“For instance, in rats antagonism of 5-HT2A (via MDL 100-907) impairs reversal performance, while 5-HT2C antagonism (with SB 242084) facilitates performance (Boulougouris et al., 2008; Boulougouris and Robbins, 2010; Nilsson et al., 2012; Furr et al., 2012b), though there is also a report of an overall impairment after…”
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Self-citation
Metadata
- Authors
- Izquierdo, A., Brigman, J. L., Radke, A. K., Rudebeck, P. H., & Holmes, A.
- Affiliations
- University of California, Los Angeles (US)
- University of New Mexico (US)
- National Institutes of Health (US)
- Icahn School of Medicine at Mount Sinai (US)
- Corresponding author
- Izquierdo, A.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2017-03
- Volume
- 345
- Pages
- 12-26
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC5018909
- OpenAlex
- W2294342312
- Cited by
- 670
- References
- 220
- Citations by year
- 2026: 66 · 2025: 93 · 2024: 89 · 2023: 69 · 2022: 77 · 2021: 79 · 2020: 68 · 2019: 47 · 2018: 36 · 2017: 31
- FWCI
- 4.47
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- UCLA Division of Life Sciences Recruitment and Retention
- National Institute on Alcohol Abuse and Alcoholism (1P50AA022534-01)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Functions and Memory
- Keywords
- reversal learning, cognitive flexibility, response inhibition, construct validity, neural basis, cortical regions, subcortical structures, neurotransmitter systems, neuropsychiatric disorders, non-human primates, rodents
- MeSH terms
- Animals, Brain, Humans, Neurons, Reversal Learning
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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