The DOI matches its Crossref record; 123 of the 123 references it cites were found in a registry or an index.
Neural circuits subserving behavioral flexibility and their relevance to schizophrenia
Abstract
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 lobe functioning. However, recent animal studies have highlighted the distinct functional roles that different subcortical systems interconnected with the prefrontal cortex (PFC) play in different forms of behavioral flexibility. This suggests that dysfunction in these circuits also contribute to the cognitive impairments in these processes observed in schizophrenia. The present review summarizes findings from studies that utilize or rodent studies rodents to elucidate the dissociable contributions that prefrontal cortical, striatal, thalamic and dopaminergic systems make to different component processes of behavioral flexibility, with an emphasis on set-shifting functions mediated by the medial PFC. We also review recent work investigating how different manipulations thought to model certain aspects of schizophrenia affect set-shifting and reversal learning. Lastly, we report novel data describing the effects of subchronic ketamine exposure on these forms of flexibility. Ketamine treatment reduced perseverative tendencies during set-shifting, but impaired reversal learning, suggesting a complex disruption of neural circuits related to the nucleus accumbens shell and orbitofrontal cortex. Viewed collectively, these findings further our understand…
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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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Blockade of NMDA Receptors and Apoptotic Neurodegeneration in the Developing Brain
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Neill, J. C., Barnes, S. A., Cook, S., Grayson, B., Idris, N. F., McLean, S. L., Snigdha, S., Rajagopal, L., & Harte, M. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.07.004 · Cited by 541
Sala, M., Braida, D., Lentini, D., Busnelli, M., Bulgheroni, E., Capurro, V., Finardi, A., Donzelli, A., Pattini, L., Rubino, T., et al. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.12.022 · Cited by 375
Animal models of psychiatric disorders
Koob, G. F., & Zimmer, A. (2012) · Handbook of clinical neurology · doi:10.1016/b978-0-444-52002-9.00009-7 · Cited by 338
Floresco, S. B. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00062 · Cited by 336
Self-citationThe mesoaccumbens dopamine in coping with stress
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Metadata
- Authors
- Floresco, S. B., Zhang, Y., & Enomoto, T.
- Affiliations
- University of British Columbia (CA)
- Corresponding author
- Floresco, Stan B.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2009-12-07
- Volume
- 204
- Issue
- 2
- Pages
- 396-409
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W2013952470
- Cited by
- 298
- References
- 123
- Citations by year
- 2026: 5 · 2025: 9 · 2024: 12 · 2023: 10 · 2022: 17 · 2021: 13 · 2020: 11 · 2019: 9 · 2018: 19 · 2017: 26 · 2016: 32 · 2015: 23 · 2014: 24 · 2013: 25 · 2012: 17
- FWCI
- 10.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- behavioral flexibility, schizophrenia, set-shifting, reversal learning, prefrontal cortex, striatum, thalamus, dopaminergic system, nucleus accumbens shell, orbitofrontal cortex, ketamine, perseveration, cognitive impairment, animal models of schizophrenia, neural circuits
- MeSH terms
- Animals, Corpus Striatum, Humans, Neural Pathways, Problem Solving, Psychomotor Performance, Reversal Learning, Schizophrenia, Schizophrenic Psychology, Thalamus, Prefrontal Cortex, Rats
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