Cited by 298Schizophrenia research and treatmentNeural and Behavioral Psychology StudiesNeurotransmitter Receptor Influence on Behavior

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Neural circuits subserving behavioral flexibility and their relevance to schizophrenia

Floresco, Stan B., Zhang, Ying, Enomoto, Takeshi·2009·Behavioural Brain Research

DOI 10.1016/j.bbr.2008.12.001

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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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Authors: Floresco, S. B., Zhang, Y., & Enomoto, T.
Affiliations: University of British Columbia (CA)
Corresponding author: Floresco, Stan B.
ORCID: Floresco, Stan B.
Zhang, Ying
Venue: Behavioural Brain Research
Publisher: Elsevier BV
Published: 2009-12-07
Volume: 204
Issue: 2
Pages: 396-409
ISSN: 0166-4328 (ISSN-L)
DOI: 10.1016/j.bbr.2008.12.001
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
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
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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Neural circuits subserving behavioral flexibility and their relevance to schizophrenia

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