The neural underpinnings of cognitive flexibility and their disruption in psychotic illness

Waltz, James A.

doi:10.1016/j.neuroscience.2016.06.005

Cited by 122Schizophrenia research and treatmentNeural and Behavioral Psychology StudiesNeurotransmitter Receptor Influence on Behavior

The neural underpinnings of cognitive flexibility and their disruption in psychotic illness

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Waltz, James A.·2017·Neuroscience

DOI 10.1016/j.neuroscience.2016.06.005PMC PMC5143214

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Abstract

Schizophrenia (SZ) has long been associated with a variety of cognitive deficits, including reduced cognitive flexibility. More recent findings, however, point to tremendous inter-individual variability among patients on measures of cognitive flexibility/set-shifting. With an eye toward shedding light on potential sources of variability in set-shifting abilities among SZ patients, I examine the neural substrates of underlying probabilistic reversal learning (PRL) - a paradigmatic measure of cognitive flexibility - as well as neuromodulatory influences upon these systems. Finally, I report on behavioral and neuroimaging studies of PRL in SZ patients, discussing the potentially influences of illness profile and antipsychotic medications on cognitive flexibility in SZ.

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Deficits in the ability to flexibly update behaviour are manifest in a wide range of neurological and psychiatric disorders, including autism, obsessive-compulsive disorder, major depressive disorder and schizophrenia.
“Deficits in the ability to flexibly update behaviour are manifest in a wide range of neurological and psychiatric disorders, including autism, obsessive–compulsive disorder, major depressive disorder and schizophrenia [23–30]”
From Linking haploinsufficiency of the autism- and schizophrenia-associated gene Cyfip1 with striatal-limbic-cortical network dysfunction and cognitive inflexibility (2024) · cites this paper as [29]
The Introduction describes cognitive-flexibility deficits in schizophrenia, and the General Conclusions describe excessive rigidity in obsessive–compulsive disorder and atypical switching in major depressive disorder. Our copy does not address autism, so it does not support that example in the cited sentence (searched: autism). (LLM, conf=0.88)
Experimental — accuracy not yet measured
Our results are in keeping with deficits in the ability to flexibly update behaviour observed in neurological and psychiatric disorders such as Parkinson's Disease, schizophrenia and autism.
“Moreover, our results are in keeping with deficits in the ability to flexibly update behaviour observed in neurological and psychiatric disorders such as Parkinson’s Disease, schizophrenia and autism [23–31].”
From Linking haploinsufficiency of the autism- and schizophrenia-associated gene Cyfip1 with striatal-limbic-cortical network dysfunction and cognitive inflexibility (2024) · cites this paper as [29]
The General Conclusions (page unavailable) describe excessive rigidity in Parkinson’s disease and altered cognitive flexibility in subgroups of people with schizophrenia. The passages do not address autism, so this source supports only part of the cited list. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Frontostriatal circuitry appears linked with variability of cognitive flexibility performance in schizophrenia, as in the general population.
“Just as in the general population, frontostriatal circuitry appears to be linked with variability of cognitive flexibility performance in schizophrenia96.”
From Cognitive and behavioural flexibility: Neural mechanisms and clinical considerations (2021) · cites this paper as [96]

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CatecholO-Methyltransferase Val158Met Polymorphism in Schizophrenia: Differential Effects of Val and Met Alleles on Cognitive Stability and Flexibility
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Dissociable effects of selective 5-HT2A and 5-HT2C receptor antagonists on serial spatial reversal learning in rats
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Discrimination learning, reversal, and set-shifting in first-episode schizophrenia: stability over six years and specific associations with medication type and disorganization syndrome
Leeson, V. C., Robbins, T. W., Matheson, E., Hutton, S. B., Ron, M. A., Barnes, T. R. E., & Joyce, E. M. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.05.016 · Cited by 219 · see citing works
In vivo PET study of 5HT2A serotonin and D2 dopamine dysfunction in drug-naive obsessive-compulsive disorder
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Dopaminergic control of cognitive flexibility in humans and animals
Klanker, M., Feenstra, M., & Denys, D. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00201 · Cited by 209 · see citing works
Serotonergic Modulation of Prefrontal Cortex during Negative Feedback in Probabilistic Reversal Learning
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A Genetically Mediated Bias in Decision Making Driven by Failure of Amygdala Control
Roiser, J. P., Martino, B. D., Tan, G. C.-Y., Kumaran, D., Seymour, B., Wood, N. W., & Dolan, R. J. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.0407-09.2009 · Cited by 199 · see citing works
Amygdala Reactivity to Emotional Faces in the Prediction of General and Medication-Specific Responses to Antidepressant Treatment in the Randomized iSPOT-D Trial
Williams, L. M., Korgaonkar, M. S., Song, Y. C., Paton, R., Eagles, S., Goldstein-Piekarski, A., Grieve, S. M., Harris, A. W. F., Usherwood, T., & Etkin, A. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.89 · Cited by 195 · see citing works
Iowa Gambling Task in schizophrenia: A review and new data in patients with schizophrenia and co-occurring cannabis use disorders
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Contribution of Working Memory to Transient Activation in Human Inferior Prefrontal Cortex during Performance of the Wisconsin Card Sorting Test
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The role of the habenular complex in the elevation of dorsal raphe nucleus serotonin and the changes in the behavioral responses produced by uncontrollable stress
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Dopamine DRD2 Polymorphism Alters Reversal Learning and Associated Neural Activity
Jocham, G., Klein, T. A., Neumann, J., von Cramon, D. Y., Reuter, M., & Ullsperger, M. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.5195-08.2009 · Cited by 178 · see citing works
Neuropsychological change in patients with schizophrenia after treatment with quetiapine or haloperidol.
Purdon, S. E., MALLA, A. K., Labelle, A., & Lit, W. (2001) · PubMed Central · Cited by 178 · see citing works
Acute tryptophan depletion in healthy volunteers enhances punishment prediction but does not affect reward prediction
Cools, R., Robinson, O. J., & Sahakian, B. (2008) · Neuropsychopharmacology · doi:10.1038/sj.npp.1301598 · Cited by 172 · see citing works
Reversal learning and dopamine: a Bayesian perspective
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Psychopharmacology of atypical antipsychotic drugs: From the receptor binding profile to neuroprotection and neurogenesis
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Neurocognitive measures of prefrontal cortical dysfunction in schizophrenia
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Frontal-Lobe Dysfunction in Schizophrenia and Obsessive-Compulsive Disorder - A Neuropsychological Study
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Genetic contributions of the serotonin transporter to social learning of fear and economic decision making
Crişan, L. G., Pană, S. E., Vulturar, R., Heilman, R. M., Szekely‐Copîndean, R. D., Drugă, B., Dragoş, N., & Miu, A. C. (2009) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsp019 · Cited by 164 · see citing works
Reinforcement and Reversal Learning in First-Episode Psychosis
Murray, G. K., Cheng, F., Clark, L., Barnett, J. H., Blackwell, A. D., Fletcher, P. C., Robbins, T. W., Bullmore, E. T., & Jones, P. B. (2008) · Schizophrenia Bulletin · doi:10.1093/schbul/sbn078 · Cited by 159 · see citing works
Executive dysfunction in first-episode schizophrenia and relationship to duration of untreated psychosis: The West London Study
Joyce, E. M., Hutton, S. B., Mutsatsa, S., Gibbins, H., Webb, E., Paul, S., Robbins, T. W., & Barnes, T. R. E. (2002) · The British Journal of Psychiatry · doi:10.1192/bjp.181.43.s38 · Cited by 158 · see citing works
Striatal dopamine mediates the interface between motivational and cognitive control in humans: evidence from genetic imaging.
Aarts, E., Roelofs, A., Franke, B., Rijpkema, M., Fernández, G., Helmich, R. C., & Cools, R. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.68 · Cited by 157 · cited 2× · see citing works
“…with striatal hyperdopaminergia, then one would expect acutely psychotic individuals to show increased reward sensitivity, reduced punishment sensitivity, and reduced cognitive flexibility, as people with more 9R alleles of the DAT1 gene appear to (Aarts et al., 2010, den Ouden et al., 2013).”
Background
A network of dopaminergic gene variations implicated as risk factors for schizophrenia.
Talkowski, M. E., Kirov, G., Bamne, M., Georgieva, L., Torres, G. E., Mansour, H. A., Chowdari, K., Milanova, V., Wood, J., McClain, L., et al. (2008) · Human Molecular Genetics · doi:10.1093/hmg/ddm347 · Cited by 154 · see citing works
Tryptophan Depletion Disrupts the Motivational Guidance of Goal-Directed Behavior as a Function of Trait Impulsivity
Cools, R., Blackwell, A. D., Clark, L., Menzies, L. A., Cox, S. M. L., & Robbins, T. W. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300704 · Cited by 145 · see citing works
Operant conditioning and the orbitofrontal cortex in schizophrenic patients: unexpected evidence for intact functioning
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Basal-corticofrontal circuits in schizophrenia and obsessive-compulsive disorder
Cavallaro, R., Cavedini, P., Mistretta, P., Bassi, T., Angelone, S. M., Ubbiali, A., & Bellodi, L. (2003) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01814-0 · Cited by 140 · see citing works
Enhancement of Spatial Reversal Learning by 5-HT<sub>2C</sub>Receptor Antagonism Is Neuroanatomically Specific
Boulougouris, V., & Robbins, T. W. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.4312-09.2010 · Cited by 136 · cited 2× · see citing works
“…receptor antagonists has also been shown to increase sensitivity to aversive outcomes, at the expense of rewarding ones, leading to a reduction in the number of perseverative errors during the performance of a reversal learning paradigm (Boulougouris et al., 2008, Boulougouris and Robbins, 2010).”
Background
Working memory constrains abstraction in schizophrenia
Glahn, D. C., Cannon, T. D., Gur, R. E., Ragland, J. D., & Gur, R. C. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00187-0 · Cited by 129 · see citing works
The Roles of Reward, Default, and Executive Control Networks in Set-Shifting Impairments in Schizophrenia
Waltz, J. A., Kasanova, Z., Ross, T. J., Salmeron, B. J., McMahon, R. P., Gold, J. M., & Stein, E. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0057257 · Cited by 122 · see citing works
Self-citation
Typical and atypical antipsychotic medications differentially affect two nondeclarative memory tasks in schizophrenic patients: a double dissociation
Beninger, R. J., Wasserman, J., Zanibbi, K., Charbonneau, D., Mangels, J. A., & Beninger, B. V. (2003) · Schizophrenia Research · doi:10.1016/s0920-9964(02)00315-8 · Cited by 121 · see citing works
Methylphenidate Has Differential Effects on Blood Oxygenation Level-Dependent Signal Related to Cognitive Subprocesses of Reversal Learning
Dodds, C. M., Muller, U., Clark, L., van Loon, A., Cools, R., & Robbins, T. W. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1153-08.2008 · Cited by 113 · see citing works
Effects of ritanserin on aversive classical conditioning in humans
Hensman, R., Guimarães, F. S., Wang, M., & Deakin, J. F. W. (1991) · Psychopharmacology · doi:10.1007/bf02244182 · Cited by 112 · see citing works
Serotoninergic mechanisms in the treatment of obsessive–compulsive disorder
Goddard, A. W., Shekhar, A., Whiteman, A. F., & McDougle, C. J. (2008) · Drug Discovery Today · doi:10.1016/j.drudis.2007.12.009 · Cited by 112 · see citing works
Dopamine D2/D3 receptor agonist quinpirole impairs spatial reversal learning in rats: investigation of D3 receptor involvement in persistent behavior
Boulougouris, V., Castañé, A., & Robbins, T. W. (2009) · Psychopharmacology · doi:10.1007/s00213-008-1341-2 · Cited by 104 · see citing works
Set-Shifting Ability and Schizophrenia: A Marker of Clinical Illness or an Intermediate Phenotype?
Ceaser, A. E., Goldberg, T. E., Egan, M. F., McMahon, R. P., Weinberger, D. R., & Gold, J. M. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2008.05.009 · Cited by 100 · see citing works
Alterations of Serotonin Transmission in Schizophrenia
Abi‐Dargham, A. (2007) · International review of neurobiology · doi:10.1016/s0074-7742(06)78005-9 · Cited by 98 · see citing works
Second generation antipsychotic-induced obsessive-compulsive symptoms in schizophrenia: a review of the experimental literature
Fonseka, T. M., Richter, M. A., & Müller, D. J. (2014) · Current Psychiatry Reports · doi:10.1007/s11920-014-0510-8 · Cited by 93 · see citing works
Probabilistic Reversal Learning in Schizophrenia: Stability of Deficits and Potential Causal Mechanisms
Reddy, L. F., Waltz, J. A., Green, M. F., Wynn, J. K., & Horan, W. P. (2016) · Schizophrenia Bulletin · doi:10.1093/schbul/sbv226 · Cited by 93 · see citing works
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The Wisconsin Card Sorting impairment in schizophrenia is evident in the first four trials
Prentice, K. J., Gold, J. M., & Buchanan, R. W. (2008) · Schizophrenia Research · doi:10.1016/j.schres.2007.07.015 · Cited by 92 · see citing works
Impaired Activation in Cognitive Control Regions Predicts Reversal Learning in Schizophrenia
Culbreth, A. J., Gold, J. M., Cools, R., & Barch, D. M. (2015) · Schizophrenia Bulletin · doi:10.1093/schbul/sbv075 · Cited by 92 · see citing works
Role of Central Serotonin in Anticipation of Rewarding and Punishing Outcomes: Effects of Selective Amygdala or Orbitofrontal 5-HT Depletion
Rygula, R., Clarke, H. F., Cardinal, R. N., Cockcroft, G. J., Xia, J., Dalley, J. W., Robbins, T. W., & Roberts, A. C. (2015) · Cerebral Cortex · doi:10.1093/cercor/bhu102 · Cited by 85 · see citing works
The role of serotonin in panic, anxiety and depression
Deakin, J. F. W. (1998) · International Clinical Psychopharmacology · doi:10.1097/00004850-199804004-00001 · Cited by 81 · see citing works
Longitudinal studies of antisaccades in antipsychotic-naive first-episode schizophrenia
Harris, M. S. H., Reilly, J. L., Keshavan, M. S., & Sweeney, J. A. (2006) · Psychological Medicine · doi:10.1017/s0033291705006756 · Cited by 80 · see citing works
Neuroleptic effects on neuropsychological test performance in schizophrenia
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The dopaminergic response to acute stress in health and psychopathology: A systematic review
Vaessen, T., Hernaus, D., Myin‐Germeys, I., & van Amelsvoort, T. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.07.008 · Cited by 76 · see citing works
Dissociable responses to punishment in distinct striatal regions during reversal learning
Robinson, O. J., Frank, M. J., Sahakian, B. J., & Cools, R. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.03.036 · Cited by 74 · see citing works
Do schizophrenia patients make more perseverative than non-perseverative errors on the Wisconsin Card Sorting Test? A meta-analytic study
Li, C. R. (2004) · Psychiatry Research · doi:10.1016/j.psychres.2004.06.016 · Cited by 71 · see citing works
Serotonin and anxiety: current models
Stein, D. J., & Stahl, S. M. (2000) · International Clinical Psychopharmacology · doi:10.1097/00004850-200008002-00002 · Cited by 69 · see citing works
Relationship of behavioural and symptomatic syndromes in schizophrenia to spatial working memory and attentional set-shifting ability
Pantelis, C., Harvey, C. A., Plant, G., Fossey, E. M., Maruff, P. T., Stuart, G. W., Brewer, W. J., Nelson, H. E., Robbins, T. W., & Barnes, T. R. E. (2004) · Psychological Medicine · doi:10.1017/s0033291703001569 · Cited by 62 · see citing works
Parsing decision making processes in prefrontal cortex: Response inhibition, overcoming learned avoidance, and reversal learning
Greening, S. G., Finger, E. C., & Mitchell, D. G. V. (2010) · NeuroImage · doi:10.1016/j.neuroimage.2010.09.017 · Cited by 62 · see citing works
Wisconsin Card Sorting Test performance in schizophrenia: the role of working memory
Hartman, M., Steketee, M. C., Silva, S. G., Lanning, K., & Andersson, C. (2002) · Schizophrenia Research · doi:10.1016/s0920-9964(02)00353-5 · Cited by 62 · see citing works
POTENTIATED PROCESSING OF NEGATIVE FEEDBACK IN DEPRESSION IS ATTENUATED BY ANHEDONIA
Mueller, E. M., Pechtel, P., Cohen, A. L., Douglas, S., & Pizzagalli, D. A. (2015) · Depression and Anxiety · doi:10.1002/da.22338 · Cited by 58 · see citing works
Integrating frequency and magnitude information in decision-making in schizophrenia: An account of patient performance on the Iowa Gambling Task
Brown, E. C., Hack, S. M., Gold, J. M., Carpenter, W. T., Fischer, B. A., Prentice, K. J., & Waltz, J. A. (2015) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2015.04.007 · Cited by 58 · see citing works
Self-citation
The role of 5-HT2C receptors in touchscreen visual reversal learning in the rat: a cross-site study
Alsiö, J., Nilsson, S. R. O., Gastambide, F., Wang, R. A. H., Dam, S. A., Mar, A. C., Tricklebank, M., & Robbins, T. W. (2015) · Psychopharmacology · doi:10.1007/s00213-015-3963-5 · Cited by 53 · see citing works
Comparison of buspirone with diazepam and fluvoxamine on aversive classical conditioning in humans
Hellewell, J. S. E., Guimarães, F. S., Wang, M. C., & Deakin, J. F. W. (1999) · Journal of Psychopharmacology · doi:10.1177/026988119901300202 · Cited by 53 · see citing works
The lesion of serotonergic neurons does not prevent antidepressant-induced reversal of escape failures produced by inescapable shocks in rats
Soubrié, P., Martin, P., Mestikawy, S. E., Thiébot, M.-H., Simon, P., & Hamon, M. (1986) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(86)90220-0 · Cited by 50 · see citing works
Differential effects of antipsychotic agents on obsessive–compulsive symptoms in schizophrenia: a longitudinal study
Schirmbeck, F. N., Rausch, F., Englisch, S., Eifler, S., Esslinger, C., Meyer‐Lindenberg, A., & Zink, M. (2012) · Journal of Psychopharmacology · doi:10.1177/0269881112463470 · Cited by 49 · see citing works
Dopamine precursor depletion improves punishment prediction during reversal learning in healthy females but not males
Robinson, O. J., Standing, H. R., DeVito, E. E., Cools, R., & Sahakian, B. J. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1880-1 · Cited by 47 · see citing works
Cognitive dysfunctions in medicated and unmedicated patients with recent-onset schizophrenia
Daban, C., Amado, I., Bourdel, M., Löo, H., Olié, J., Poirier, M. F., & Krebs, M. (2004) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2004.09.001 · Cited by 45 · see citing works
Novel Factor-Based Symptom Scores in Treatment Resistant Schizophrenia Implications for Clinical Trials
McMahon, R. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00387-6 · Cited by 43 · see citing works
Lateral habenula as a link between dopaminergic and serotonergic systems contributes to depressive symptoms in Parkinson's disease
Luo, X., Zhang, B. L., Li, J. C., Yang, Y., Sun, Y., & Zhao, H. (2014) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2014.11.006 · Cited by 42 · see citing works
Corticostriatothalamic reward prediction error signals and executive control in late-life depression
Dombrovski, A. Y., Szanto, K., Clark, L., Aizenstein, H. J., Chase, H. W., Reynolds, C. F., & Siegle, G. J. (2015) · Psychological Medicine · doi:10.1017/s0033291714002517 · Cited by 41 · see citing works
The effect of melperone, an atypical antipsychotic drug, on cognitive function in schizophrenia
Sumiyoshi, T., Jayathilake, K., & Meltzer, H. Y. (2002) · Schizophrenia Research · doi:10.1016/s0920-9964(01)00329-2 · Cited by 38 · see citing works
Neuroimaging of Serotonin System in Anxiety Disorders
Maron, E., Nutt, D., & Shlik, J. (2012) · Current Pharmaceutical Design · doi:10.2174/138161212803530844 · Cited by 36 · see citing works
Abnormal modulation of reward versus punishment learning by a dopamine D2-receptor antagonist in pathological gamblers
Janssen, L. K., Sescousse, G., Hashemi, M. M., Timmer, M. H. M., ter Huurne, N. P., Geurts, D. E. M., & Cools, R. (2015) · Psychopharmacology · doi:10.1007/s00213-015-3986-y · Cited by 35 · see citing works
The lateral habenula regulates defensive behaviors through changes in 5-HT-mediated neurotransmission in the dorsal periaqueductal gray matter
Pobbe, R. L. H., & Zangrossi, H. (2010) · Neuroscience Letters · doi:10.1016/j.neulet.2010.05.021 · Cited by 35 · see citing works
Identifying serotonergic mechanisms underlying the corticolimbic response to threat in humans
Fisher, P. M., & Hariri, A. R. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2012.0192 · Cited by 33 · see citing works
Performance on the Wisconsin Card Sorting Test in schizophrenia: Perseveration in clinical subtypes
Abbruzzese, M., Ferri, S., & Scarone, S. (1996) · Psychiatry Research · doi:10.1016/0165-1781(96)02927-7 · Cited by 31 · see citing works
Death anxiety: “State” or “trait”?
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Effects of the 5HT antagonist cyproheptadine on neuropsychological function in chronic schizophrenia
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Risperidone Treatment of Schizophrenia: Improvement in Psychopathology and Neuropsychological Tests
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Buspirone decreases physiological reactivity to unconditioned and conditioned aversive stimuli
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Frontal and callosal neuropsychological performances in schizophrenia
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Common and distinct neural effects of risperidone and olanzapine during procedural learning in schizophrenia: a randomised longitudinal fMRI study
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Cognitive and behavioural flexibility: Neural mechanisms and clinical considerations
Uddin, L. Q. (2021) · Nature Reviews Neuroscience · doi:10.1038/s41583-021-00428-w · Cited by 698 · see citing works
Dopamine, psychosis and schizophrenia: the widening gap between basic and clinical neuroscience
Kesby, J., Eyles, D., McGrath, J., & Scott, J. G. (2018) · Translational Psychiatry · doi:10.1038/s41398-017-0071-9 · Cited by 331 · see citing works
Towards an understanding of psychedelic-induced neuroplasticity
Calder, A. E., & Hasler, G. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-022-01389-z · Cited by 313 · see citing works
Reset of hippocampal–prefrontal circuitry facilitates learning
Park, A. J., Harris, A. Z., Martyniuk, K. M., Chang, C., Abbas, A. I., Lowes, D. C., Kellendonk, C., Gogos, J. A., & Gordon, J. A. (2021) · Nature · doi:10.1038/s41586-021-03272-1 · Cited by 153 · see citing works
Paranoia as a deficit in non-social belief updating
Reed, E., Uddenberg, S., Suthaharan, P., Mathys, C. D., Taylor, J. R., Groman, S. M., & Corlett, P. R. (2020) · eLife · doi:10.7554/elife.56345 · Cited by 135 · see citing works
Predictive processing, source monitoring, and psychosis
Griffin, J. D., & Fletcher, P. C. (2017) · Annual Review of Clinical Psychology · doi:10.1146/annurev-clinpsy-032816-045145 · Cited by 133 · see citing works
Dysregulation of Midbrain Dopamine System and the Pathophysiology of Schizophrenia
Sonnenschein, S. F., Gomes, F. V., & Grace, A. A. (2020) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2020.00613 · Cited by 132 · see citing works
From Gene to Behavior: L-Type Calcium Channel Mechanisms Underlying Neuropsychiatric Symptoms
Kabir, Z. D., Martínez-Rivera, A., & Rajadhyaksha, A. M. (2017) · Neurotherapeutics · doi:10.1007/s13311-017-0532-0 · Cited by 125 · see citing works
Towards a Unifying Cognitive, Neurophysiological, and Computational Neuroscience Account of Schizophrenia
Heinz, A., Murray, G. K., Schlagenhauf, F., Sterzer, P., Grace, A. A., & Waltz, J. A. (2018) · Schizophrenia Bulletin · doi:10.1093/schbul/sby154 · Cited by 118 · see citing works
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Cognitive flexibility: Impact on entrepreneurial intentions
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Authors: Waltz, J. A.
Affiliations: University of Maryland, Baltimore (US)
Corresponding author: Waltz, James A.
ORCID: Waltz, James A.
Venue: Neuroscience
Publisher: Elsevier BV
Published: 2017-03
Volume: 345
Pages: 203-217
ISSN: 0306-4522 (ISSN-L)
DOI: 10.1016/j.neuroscience.2016.06.005
PMC: PMC5143214
OpenAlex: W2411740764
Cited by: 122
References: 159
Citations by year: 2026: 17 · 2025: 14 · 2024: 7 · 2023: 14 · 2022: 13 · 2021: 22 · 2020: 10 · 2019: 7 · 2018: 7 · 2017: 9 · 2016: 2
FWCI: 1.19
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Neuroscience (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health (K12 RR023250, R01 MH094460, R01 MH080066)
NIDA-IRP
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: cognitive flexibility, schizophrenia, probabilistic reversal learning, set-shifting, interindividual variability, neural correlates, neuromodulation, antipsychotic drugs, cognitive impairment
MeSH terms: Animals, Brain, Cognition, Humans, Neural Pathways, Psychotic Disorders, Reversal Learning, Schizophrenia, Schizophrenic Psychology, Executive Function

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The neural underpinnings of cognitive flexibility and their disruption in psychotic illness

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