Demystifying cognitive flexibility: Implications for clinical and developmental neuroscience
Open accessAbstract
Cognitive flexibility, the readiness with which one can selectively switch between mental processes to generate appropriate behavioral responses, develops in a protracted manner and is compromised in several prevalent neurodevelopmental disorders. It is unclear whether cognitive flexibility arises from neural substrates distinct from the executive control network (ECN) or from the interplay of nodes within this and other networks. Here we review neuroimaging studies of cognitive flexibility, focusing on set shifting and task switching. We propose that more consistent operationalization and study of cognitive flexibility is required in clinical and developmental neuroscience. We suggest that an important avenue for future research is the characterization of the relationship between neural flexibility and cognitive flexibility in typical and atypical development.
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The Wisconsin Card Sorting Test (WCST) assesses set-shifting.
“The WCST assesses set-shifting. Participants must adapt their strategy to changing criteria such as color or shape – a core aspect of cognitive flexibility (118).”
From Neural mechanisms underlying cognitive inflexibility in obsessive-compulsive disorder: a review (2026) · cites this paper as [118]
In “Defining and measuring cognitive flexibility” (page unavailable), the paper describes set-shifting as changing rules or attending to features such as shape and color, and calls it a form of cognitive flexibility. It does not identify the WCST or state that the WCST assesses set-shifting (searched: “Wisconsin Card Sorting Test” and “WCST”). (LLM, conf=0.82)
Experimental — accuracy not yet measuredSuch dysregulation might be partially reversible via CBTs, which aim to improve psychological inflexibility, possibly mediated by the AI, ACC, and dlPFC.
“Such dysregulation might be partially reversible via CBTs, which aim to improve psychological inflexibility, possibly mediated by the AI, ACC, and dorsolateral prefrontal cortex (dlPFC) (Dajani and Uddin 2015).”
From Baseline Functional Connectivity of the Mesolimbic, Salience, and Sensorimotor Systems Predicts Responses to Psychological Therapies for Chronic Low Back Pain With Comorbid Depression: A Functional MRI Study (2025) · cites this paper as Dajani and Uddin 2015
The “Brain networks underlying cognitive flexibility” section identifies the AI, ACC, and dlPFC as regions involved in cognitive flexibility. Our copy does not support the further claim that CBT can partially reverse dysregulation or that its effects are mediated by those regions; a search for CBT and intervention-related terms found no such passage. Page numbers were unavailable. (LLM, conf=0.88)
Experimental — accuracy not yet measuredCF is a rich construct that has a notable and well-established history.
“it is a rich construct that has a notable and well-established history (Dajani & Uddin, 2015).”
From Defining and measuring “psychological flexibility”: A narrative scoping review of diverse flexibility and rigidity constructs and perspectives (2021) · cites this paper as Dajani & Uddin, 2015
The ‘Defining and measuring cognitive flexibility’ section describes the construct in multiple ways, and the References include a 1962 work on cognitive flexibility, supporting its breadth and history. But the ‘Significance of cognitive flexibility’ section says rigorous examination of the construct has been elusive, so the paper does not support calling that history well-established without qualification. Page numbers were not available in our copy. (LLM, conf=0.82)
Experimental — accuracy not yet measuredExecutive functions encompass planning for future goals, inhibiting maladaptive responses, maintaining and manipulating information in working memory, and flexibly adapting behaviors to changes in the environment.
“EFs encompass several subdomains, including planning for future goals, inhibiting maladaptive responses, maintaining and manipulating information in working memory, and flexibly adapting behaviors to changes in the environment6.”
From Heterogeneity of executive functions among comorbid neurodevelopmental disorders (2016) · cites this paper as [6]
Large-scale functional brain networks that include lateral and orbital frontoparietal, midcingulo-insular, and frontostriatal regions support flexibility throughout life.
“This work has identified large-scale functional brain networks encompassing lateral and orbital frontoparietal, midcingulo-insular and frontostriatal regions that support flexibility across the lifespan.”
From Cognitive and behavioural flexibility: Neural mechanisms and clinical considerations (2021) · cites this paper as [20]
Cognitive flexibility is hard to isolate because it depends on several executive-function components acting together.
“Cognitive flexibility is difficult to isolate, as it requires the confluence of several aspects of executive function20,28.”
From Cognitive and behavioural flexibility: Neural mechanisms and clinical considerations (2021) · cites this paper as [20]
Human functional neuroimaging research indicates that the lateral frontoparietal and midcingulo-insular networks are centrally involved in executive function and cognitive flexibility.
“A large body of literature on human functional neuroimaging studies using task-switching and set-shifting paradigms points to a central role for the lateral frontoparietal network (L-FPN) and the midcingulo-insular network (M-CIN) in supporting executive function and cognitive flexibility20,30.”
From Cognitive and behavioural flexibility: Neural mechanisms and clinical considerations (2021) · cites this paper as [20]
Decades of functional neuroimaging work have delineated the executive control/lateral frontoparietal and salience/midcingulo-insular networks as brain networks underlying executive functions that contribute to cognitive flexibility.
“Decades of functional neuroimaging work has delineated brain networks underlying EFs that contribute to cognitive flexibility (21,22), namely the executive control/lateral frontoparietal (L-FPN) and salience/midcingulo-insular networks (M-CIN) (23–25).”
From Brain Mechanisms Supporting Flexible Cognition and Behavior in Adolescents With Autism Spectrum Disorder (2021) · cites this paper as [25]
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- Authors
- Dajani, D. R., & Uddin, L. Q.
- Affiliations
- University of Miami (US)
- Corresponding author
- Uddin, Lucina Q.
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2015-09
- Volume
- 38
- Issue
- 9
- Pages
- 571-578
- ISSN
- 0166-2236 (ISSN-L)
- PMC
- PMC5414037
- OpenAlex
- W1783354124
- Cited by
- 1,046
- References
- 89
- Citations by year
- 2026: 134 · 2025: 158 · 2024: 147 · 2023: 135 · 2022: 118 · 2021: 127 · 2020: 72 · 2019: 66 · 2018: 51 · 2017: 19 · 2016: 15 · 2015: 2 · 2014: 1
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Alliance for Research on Schizophrenia and Depression
- National Institute of Mental Health (K01MH092288, R01MH107549)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Functions and Memory
- Social Sciences › Psychology › Neuropsychology and Physiological Psychology › Developmental and Educational Neuropsychology
- Keywords
- cognitive flexibility, frontoparietal network, set-shifting, task switching, neural flexibility, neurodevelopmental disorders, developmental neuroscience, clinical neuroscience
- MeSH terms
- Attention, Brain, Cognition, Humans, Inhibition, Psychological, Memory, Short-Term, Executive Function
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